Abstract

Background: Ischemia/reperfusion (I/R) is often a complication of bleeding shock, renal dysfunction
and renal vessel operation. Nitric oxide (NO) as an important vasodilator is produced by endothelial
cells. NO stimulates the generation of cyclic guanosine monophosphate (cGMP). Phosphodiesterase
(PDE) is an intracellular enzyme which hydrolyzes cGMP into an inactive metabolite. It effectively
decreases cGMP level. PDE is an intracellular enzyme which hydrolyzes cGMP into an inactive
metabolite. It effectively decreases cGMP level. Therefore, an inhibition of PDE can increase cGMP
level. PDE5 inhibitor is a compound which inhibits or acts antagonistically against biosynthesis
or act of PDE. PDE5 inhibitor is now commonly used for the treatment of pulmonary artery
hypertension and erectile dysfunction. According to some latest researches, long-acting PDE5
inhibitor (Tadalafil) reduces renal I/R injury in experiments with Wistar rats.

Objectives: The purpose of this study was to determine the effect of long-acting PDE5 inhibitor on
renal I/R injury in Wistar rats.

Materials and Methods: Rats were divided into three groups; sham group, a right nephrectomy was
performed. Control group, a right nephrectomy was performed followed by an occlusion on left
renal pedicle for 60 minutes and a perfusion was performed for 60 minutes. Tadalafil group; the
same treatment was performed as to group control, plus administering tadalafil as a PDE5 inhibitor
(10 mg/kg), given by a nasogastric tube 60 minutes before the operation. A left nephrectomy was
performed on the mice to determine the value of cystatin C level and histopathology.

Results: The mean necrosis of tubular renal cells indicates that highest mean necrosis of tubular renal
cells was at group control (mean score, 8.6±0.84), and the lowest mean necrosis of tubular renal
cells was at sham group (mean score, 4.4±0.52) which indicates a significant difference between the
sham and control groups (P<0.05). For the tadalafil group mean score of renal tubular necrosis cell
was 6.9±1.45, which also indicates a significant difference between this group with sham group and
control (P<0.05). Highest mean cystatin C levels related to group control, mean score was 1.51 ±
0.13 mg/dL, which indicates a significant difference with the sham group (P<0.05), but there is no
significant difference with the tadalafil group.

Conclusion: The results of this study showed that the administration of PDE5 inhibitor (tadalafil)
improves reperfusion ischemic injury. Although it did not decrease the level of cystatin C, it
significantly reduced tubular necrosis.